Successful Treatment of Massive Pulmonary Thromboembolism with Reteplase: Case Series.

Massive pulmonary thromboembolism (PTE) has an increased risk of mortality. Thrombolytic therapy is the accepted treatment. Reteplase, a variant of tissue plasminogen activator, has been used in acute myocardial infarction with acceptable safety and efficacy, but studies in massive PTE are rare. In this study we report five cases of successful treatment of massive PTE with reteplase.


INTRODUCTION
Acute pulmonary thromboembolism (PTE) is a common and potentially lethal form of venous thromboembolism (VTE); PTE typically has a poor prognosis with a high mortality rate despite advances in diagnosis and therapy (1). Acute PTE has been classified into three groups: non-massive or low risk, submassive or moderate/intermediate risk, and massive or high risk.
These two groups (massive and submassive PTE) are at increased risk of mortality. The rapid reinstitution of sufficient pulmonary blood flow and right ventricular unloading is important to save the patient's life (3,4).
Therapeutic methods in patients with massive PTE and hemodynamic collapse include thrombolytic agents, catheter-based thrombus fragmentation or aspiration, and surgical embolectomy (5). Thrombolytic therapy is widely used as a first line treatment with satisfactory results (6).
Recent meta-analysis indicated that thrombolysis was associated with a significant reduction of all-cause mortality. However, following thrombolysis these patients are at risk of major bleeding and fatal or intracranial hemorrhage (7). Different thrombolytic agents have been introduced including alteplase, reteplase and tenecteplase.
Reteplase is a variant of tissue plasminogen activator with an extended circulation time, lower fibrin affinity, and greater susceptibility to plasminogen inhibitors (8).
Although the effectiveness of reteplase in acute myocardial infarction is known, few case reports and case studies have reported its utility in acute massive and submassive PTE (9)(10)(11)(12). Reteplase has been used in most centers to treat massive PTE, but it is not fully approved. In this study, we report a series of 5 cases with massive PTE treated with reteplase.

MATERIALS AND METHODS
In this retrospective study, five consecutive patients with massive PTE admitted to Imam Khomeini Hospital, Patient was treated conservatively and was extubate in the next three days. Control brain imaging showed no further hemorrhage. Patient was discharged after 10 days with no further complications.

Case 4
The fourth patient was a 49-year-old male, a known case of COPD and ischemic heart disease with no predisposing factor, presenting with chest pain and vertigo in the last two days. RV enlargement and dysfunction and SPAP of 50 mmHg were reported in the primary echocardiography, which improved in the post treatment follow-up echocardiography with normal RV function.
Patient had no complications and discharged after 6 days.

Case 5
The

DISCUSSION
Massive PE is complicated by hemodynamic instability and RV dysfunction which has poor prognosis; therefore, early diagnosis, prompt risk stratification, and aggressive therapeutic strategies are necessary to reduce the mortality rate (1,2). Rapid restoration of the RV function and pulmonary blood flow will improve patient's survival (3,4). In the study of Liu and Wang (12), cerebral hemorrhage was seen in one case (5.5%). Zhao et al. (9) also reported one case of thrombolysis-related hemoptysis in their patients with sub-massive PTE. Theron and Laidlow (10) reported no bleeding in their study. Similarly, Tebbe et al. (11) reported no intracranial hemorrhage in their cases.
Previous studies have shown that reteplase has similar risk of bleeding as other fibrin-specific thrombolytic agents (8,11); Tebbe et al. (11) noted that reteplase has similar safety and efficacy to alteplase in massive PTE.
No mortality was reported among our cases. Similarly, Zhao et al. (9) reported no mortality in hospital and during follow-up. However, 5 cases (27.5%) died in the study of Liu and Wang (12).

CONCLUSION
In conclusion, reteplase is effective in the treatment of patients with massive PTE and the benefits of reteplase are higher than its risk of bleeding.